Changes in Brain Neuroimmunology Following Injury and Disease

Abstract

The nervous and immune systems are intimately related in the brain and in the periphery, where changes to one affect the other and vice-versa. Immune cells are responsible for sculpting and pruning neuronal synapses, and play key roles in neuro-development and neurological disease pathology. The immune composition of the brain is tightly regulated from the periphery through the blood-brain barrier (BBB), whose maintenance is driven to a significant extent by extracellular matrix (ECM) components. After a brain insult, the BBB can become disrupted and the composition of the ECM can change. These changes, and the resulting immune infiltration, can have detrimental effects on neurophysiology and are the hallmarks of several diseases. In this review, we discuss some processes that may occur after insult, and potential consequences to brain neuroimmunology and disease progression. We then highlight future research directions and opportunities for further tool development to probe the neuro-immune interface.

Molecular Profiling of the Hippocampus of Children with Autism Spectrum Disorder

“…1 and Supplemental Table 1). Furthermore, ECM molecules are also highly involved in blood-brain barrier (BBB) regulation 93 . Our findings suggesting altered BBB composition in the hippocampus of children with ASD are in line with recent evidence for BBB dysfunction in ASD 94, 95 .…”

Systemic immune responses after ischemic stroke: From the center to the periphery

“…The nervous and immune systems interact with and regulate each other from the embryonic stage ( 9 , 10 ). As research has progressed, the classical concept of separation of the CNS and peripheral immune system is gradually giving way to dynamic intermodulation ( 11 ).…”

Reprogramming brain immunosurveillance with engineered cytokines

“…Abstract: Immune surveillance of the brain is regulated by resident non-neuronal cells and the blood-brain barrier. 1 Dysregulation of immunosurveillance is a hallmark feature of several diseases [2][3][4][5] including brain tumors 6 that interact with and rely heavily on immune cells, 7 suggesting that disrupting the neuroimmunology of tumors could slow their progression. Yet few tools are available to control brain immunology in vivo with local precision, and fewer yet are used for therapeutic intervention.…”

“…Yet few tools are available to control brain immunology in vivo with local precision, and fewer yet are used for therapeutic intervention. 2 Here, we propose engineered cytokines as a neuroimmune-modulation platform. We demonstrate that the residence time of cytokines in the brain can be tuned by binding them to the extracellular matrix or synthetic scaffolds.…”

“…Classical notions of brain immune privilege and isolation are being challenged as increasing evidence reveals mechanisms of brain immunosurveillance by peripheral immune cells and antigen drainage through meningeal lymphatics. 2,3,8,9 Recent studies demonstrated that enhancing lym-phatic drainage through lymphangiogenic factor VEGF-C can improve monoclonal antibody therapy targeting amyloid beta in Alzheimer’s disease 5 or immune checkpoint blockade for brain cancer immunotherapy. 6 Immunotherapy against established brain tumors could also be achieved with patientspecific chimeric antigen receptor (CAR) T cells, 10 and in a recent clinical trial, CAR T cell immunotherapy was shown to improve clinical outcomes for children diagnosed with lethal pediatric gliomas.…”